1,2-Dimethoxyethane → HCID 86664834, compound

HRID 1628286Notes

Reaction equation

HRID 1628286 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6](B(O)O)[CH:5]=[CH:4][N:3]=1.Br[C:12]1[CH:13]=[C:14]([NH:19][C:20](=[O:37])[C@@H:21]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:15]=[C:16]([Cl:18])[CH:17]=1.[F-].[Cs+].COCCOC>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:18][C:16]1[CH:15]=[C:14]([NH:19][C:20](=[O:37])[C@@H:21]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:33])([CH3:35])[CH3:34])[CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:13]=[C:12]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([CH3:1])[CH:7]=2)[CH:17]=1

Participants

6

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 25953Cesium fluorideHCID 41926642-Methylpyridine-4-boronic acidHCID 67497166HCID 67497166, compound

Product 1

HCID 86664834HCID 86664834, compoundYield 66.2%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
85 °C

Procedure

2-methylpyridin-4-ylboronic acid (327 mg, 2.39 mmol), (S)-tert-butyl 1-(3-bromo-5-chlorophenylamino)-1-oxo-3-phenylpropan-2-ylcarbamate (542 mg, 1.19 mmol), tetrakis(triphenylphosphine)palladium (345 mg, 0.30 mmol), cesium fluoride (544 mg, 3.58 mmol) were added to a vial then DME (4778 μl, 1194 μmol) was added and the mixture was heated to 85° C. for 8 h. The reaction was loaded and purified on Phenomenex Geminni C18 HPLC 50 mm×250 mm running ACN/Water/0.1% TFA in a linear gradient. The fractions containing the desired product were combined and concentrated to afford tert-butyl (S)-1-(3-chloro-5-(2-methylpyridin-4-yl)phenylamino)-1-oxo-3-phenylpropan-2-ylcarbamate (367 mg, 66% yield). tert-butyl (S)-1-(3-chloro-5-(2-methylpyridin-4-yl)phenylamino)-1-oxo-3-phenylpropan-2-ylcarbamate (367 mg, 0.78 mmol) was dissolved in DCM (3 mL) and TFA (1 mL) add stirred for 3 h. The solution was concentrated to afford (2S)-2-amino-N-(3-chloro-5-(2-methylpyridin-4-yl)phenyl)-3-phenylpropanamide (280 mg, 99%).

Workup

  1. additionwas added
  2. custompurified on Phenomenex Geminni C18 HPLC 50 mm×250 mm
  3. additionThe fractions containing the desired product
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-79dd22eabd684190ba169f05a87ae1f6
Source dataset
uspto-grants-2014_07
Patent number
US08785468B2

Reaction notes

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